Avacopan as an additional therapeutic intervention to promote renal recovery in severe ANCA-associated vasculitis: A case report.

Avacopan, a C5a receptor antagonist (C5aR) presents a new therapeutic option to improve outcomes in ANCA-associated vasculitis (AAV). Here we present a case report of a patient initially requiring kidney replacement therapy (KRT), where avacopan was added as an additional adjunctive therapeutic agent late in the treatment course.

A review of nanocrystalline cellulose suspensions: Rheology, liquid crystal ordering and colloidal phase behaviour.

Nanocrystalline cellulose (NCC) is a colloidal rigid rod, referred to by various terms in the literature including cellulose whisker (CW) and cellulose nanocrystal (CNC). These charged colloidal rods exhibit complex colloidal phase and rheological behaviours in aqueous suspensions, that are dependent on volume fraction and interparticle forces. A major shortcoming in the literature of NCC is that the dimensions and morphology of NCC particles vary significantly with the type of raw material and manufacturing conditions, which causes inconsistencies in suspension rheology and colloidal behaviours reported between different works. In this review, we consider the theory and experimentally-determined rheological and colloidal phase behaviours of charged rod suspensions in general, with a focus in particular on NCC. Dilute and semi-dilute NCC suspensions are isotropic liquids, in which NCC particles follow diffusional dynamics. The rheology of these isotropic NCC suspensions can be described by theoretical models that account for the effects of rod dimensions and surface charge, including those based on Doi and Edwards' theory. With increasing NCC concentration, the isotropic phase can undergo a transition to a liquid crystalline state (isotropic-nematic transition) or a transition to a dynamically arrested solid (liquid-solid transition). The liquid crystal ordering and gelation/glass transition are of particular interest because they respectively form an ordered structure and allow a solid-like mechanical response at relatively low solids fraction. For conditions at which the isotropic-nematic and liquid-solid transitions coincide, the formation of an anisotropic structure within a soft solid suspension is possible. Investigation of these two competing transitions led to the discovery of liquid crystal re-entrancy and existence of an anisotropic soft solid (liquid crystal hydroglass, LCH). LCH has a biphasic structure with an attractive glass matrix and a co-existing liquid crystal phase, providing similar viscoelastic properties to hydrogels but permitting reversible orientation of the colloidal rods in the liquid crystalline phase by shear forces; i.e. their structural ordering is programmable. The liquid crystal transition and gelation/glass transitions are quantitatively dependent on rod dimensions i.e. respectively proportional to L2D and L/D. Phase transitions in NCC suspensions including liquid crystal re-entrancy and formation of LCH can be fully described as a function of rod dimension, volume fraction and interparticle forces. This behaviour is independent of NCC source, allowing development of a generalised phased diagram in which separately-reported phase transitions converge to consistent phase boundaries. This validates a key hypothesis for the study of NCC suspensions, that variation in NCC concentration and interparticle forces can explain the complex phase behaviours observed within suspensions formulated using NCC obtained from different sources.

Structure and rheology of liquid crystal hydroglass formed in aqueous nanocrystalline cellulose suspensions.

HYPOTHESIS: Liquid crystal hydroglass (LCH) is a biphasic soft material with flow programmable anisotropy that forms via phase separation in suspensions of charged colloidal rods upon increases in ionic strength. The unique structure and rheology of the LCH gel formed using nanocrystalline cellulose (NCC) is hypothesised to be dependent on colloidal stability that is modulated using specific ion effects arising from Hofmeister phenomena. EXPERIMENTS: LCHs are prepared in NCC suspensions in aqueous media containing varying levels of sodium chloride (NaCl) or sodium thiocyanate (NaSCN). The NCC suspensions are characterised using rheology and structural analysis techniques that includes polarised optical microscopy, zeta potential, dynamic light scattering and small-angle X-ray scattering. FINDINGS: The two salts have a profound effect on the formation process and structure of the LCH. Differences in network density and size of the liquid crystal domains are observed within the LCH for each of the salts, which is associated with the strength of interaction between NCC particles during LCH formation. In comparison to Cl- at the same salinity, the chaotropic nature of the weakly hydrated SCN- enhances colloidal stability by rendering NCC particles more hydrated and repulsive, but this also leads to weaker gel strength of the LCH. The results suggest that salts are a means in which to control the formation, structure and rheology of these anisotropic soft materials.

Liquid crystal hydroglass formed via phase separation of nanocellulose colloidal rods.

A new anisotropic soft material - a liquid crystal 'hydroglass' (LCH) - is created from aqueous suspensions of nanocrystalline cellulose (NCC) colloidal rods. Under specific conditions, the NCC suspension separates into a colloid-rich attractive glass matrix phase and a coexisting liquid crystal phase. LCH provides similar viscoelastic properties to polymer and colloidal gels, but permits reversibly-orientating the colloidal rods through shear forces.

"Liquid, gel and soft glass" phase transitions and rheology of nanocrystalline cellulose suspensions as a function of concentration and salinity.

The colloidal size and rod morphology of nanocrystalline cellulose (NCC) lead to suspensions with useful phase and gelation behaviours as well as complex rheologies. However, these have not been comprehensively evaluated previously. Here we report the detailed phase behaviour of sulphonated NCC aqueous suspensions as a function of concentration and salinity. Four phases - liquid, viscoelastic, repulsive glass and attractive glass/gel - are identified in terms of their distinct rheological behaviours. The liquid-solid transitions (LSTs) are determined rheologically, and these are supported by a simplified model based on the DLVO theory that indicates the importance of charge in determining the phase behaviour. Rheology is also used to investigate the solid-solid transition from a repulsive glass to an attractive gel with increasing salt at high NCC concentrations. A time-dependent aging phenomenon is observed in suspensions with a composition just below the LSTs, and the implications of this on the dynamics occurring during gelation processes are discussed. This work can be directly applied to the development of structure-function relationships and the expanding utilisation of NCC suspensions, whilst also providing a basis for the study of charged colloidal rods more generally and evaluation of theoretical models.

Rheology and microstructure of aqueous suspensions of nanocrystalline cellulose rods.

HYPOTHESIS: Nanocrystalline cellulose (NCC) is a negatively charged rod-like colloid obtained from the hydrolysis of plant material. It is thus expected that NCC suspensions display a rich set of phase behaviour with salt and pH because of its anisotropic shape and electrical double layer that gives rise to liquid crystallinity and self-assembly respectively. It should thus be possible to tune the rheological properties of NCC suspensions for a wide variety of end-use applications. EXPERIMENTS: Rheology and structural analysis techniques are used to characterise surface-sulphated NCC suspensions as a function of pH, salinity (NaCl) and NCC concentration. Structural techniques include atomic force microscopy, Zeta potential, dynamic light scattering, and scanning electron microscopy. FINDINGS: A phase diagram is developed based on the structure-rheology measurements showing various states of NCC that form as a function of salt and NCC concentration, which go well beyond those previously reported. This extended range of conditions reveals regions where the suspension is a viscous fluid and viscoelastic soft solid, as well as regions of instability that is suggested to arise when there is sufficient salt to reduce the electrical double layer (as explained qualitatively using DLVO theory) but insufficient NCC to form a load bearing network.